In experimental animal models, oral administration of protein antigens induces a state of antigen-specific immunologic tolerance known as oral tolerance. Oral antigen administration can both prevent and treat experimentally induced autoimmune disease in animal models, and may thus have the potential for treating human autoimmune diseases. Previous studies from our laboratory have demonstrated that oral administration of the protein antigen keyhole limpet hemocyanin (KLH) prior to systemic immunization with KLH can suppress some facets of the systemic immune response to KLH, and may induce immune deviation. The purpose of this study was to determine whether immune tolerance to KLH could be induced in human subjects who had been immunized previously with KLH. Sixteen adult subjects, consisting of equal numbers of males and females, were enrolled in the study; all subjects successfully completed the protocol. Subjects were immunized i.m. with KLH without adjuvant at the beginning of the study and were instructed to consume 100 mg per day of either KLH or chicken ovalbumin contained in gelatin capsules for 42 consecutive days commencing 7 days after the initial immunization. Subjects were given an i.m. boost with KLH on day 56. Peripheral blood was drawn at intervals throughout the study and assayed for antibody, B cell, and T cell responses to KLH and ovalbumin.